Karen was on the Thanksgiving holiday vacation from high school on November 25, 1997 in Eureka, California. She departed from her place of employment, the Coastal Family Development Center, during the afternoon hours. Karen's aunt, Annie Casper, was her legal guardian and owned a shoe store inside Bayshore Mall. The shopping center was in the 3300 block of Broadway Street, approximately one mile from Karen's place of employment. She briefly visited her aunt's business before departing from the mall at approximately 2:45 p.m. Karen was last seen walking towards West Sonoma Street shortly afterwards. She has never been heard from again.

A witness stated that Karen may have entered an unidentified light blue four-door 1976 to 1978 sedan, which was possibly a Ford Grenada, a Mercury Monarch, or a Nissan. The vehicle had California license plates and "Eureka" imprinted on the rear plate's frame. The driver of the car is described as a Caucasian male, approximately 60 to 70 years old, with balding light gray or sandy blonde hair. The unidentified man had green or gray eyes and a large-sized nose that appeared to have been previously broken. He had a small build and wore eyeglasses. The driver was wearing a long-sleeved button-down light blue shirt. Sketches of both the driver and vehicle are posted below this case summary. The driver is wanted for questioning as a possible witness in Karen's case. The witness claimed that the car pulled across Broadway Street and nearly hit him before stopping for a girl matching Karen's description.

Authorities identified a vehicle similar to the car reported by the witness shortly after Karen vanished. The owner passed a polygraph exam and was cleared of any potential involvement in her case. Confessed murderer Wayne Adam Ford, who killed several women in California during the 1990s, denied any involvement in Karen's disappearance. His photo is posted below this case summary. Ford turned himself into authorities one year after Karen vanished. He has never been charged in connection with her case. His photo is posted below this case summary.

Robert Durst apparently visited Casper's store several times in March 1998, four months after Karen disappeared, and he resembles the sketch of the man wanted for questioning in Karen's case. His photo is posted below this case summary. Robert's first wife, Kathleen Durst, disappeared from New York in 1982. Her case remains unsolved and Robert is considered the prime suspect, although he has never been charged in connection with her case. Robert was charged with the 2001 Texas homicide of Morris Black. He claimed he murdered Black in self-defense, and was acquitted in 2003. In 2015, he was charged with murder in the 2000 shooting death of Susan Berman. Investigators looked into the possibility that Robert was in the Eureka area at the time of Karen's disappearance, but he has never been charged with any involvement. They've ruled him out as a suspect in the 1997 disappearance of
Kristen Modaferri from San Francisco, but he's being looked at in the 1971 disappearance of
Lynne Schulze from Middlebury, Vermont. Robert and Kathleen owned a health food store in Middlebury at the time of Schulze's disappearance.

Karen's parents divorced not long after she was born and her mother raised her and her brother alone. Karen moved in with her aunt and uncle when she was thirteen. She had liberal views in 1997 and was passionate about politics, the environment and children. She was a good student and within a semester of graduating high school by the time of her disappearance; she planned to attend Humboldt State University and possibly study law or political science. Her case remains unsolved.